Squamous cell carcinomas, including those of the mouth and oropharynx, comprise more than 90% of all cancers affecting these tissues (1). Simply providing universal, expert clinical examination would not meet the need for improved early diagnosis of oral/oropharyngeal cancer. Development and validation of an accurate test to assess risk of oral/oropharyngeal cancer has the potential to improve therapeutic outcomes, reduce associated morbidity, and reduce treatment costs. The combination of salivary rinse soluble CD44 (SolCD44) and salivary rinse total protein identified by Vigilant Biosciences has shown to be much more accurate in the detection of oral cancers than conventional detection techniques (5,30,31) In addition, increased SolCD44 is independently associated with poor prognosis in these cancers. This project will 1) continue the development of a unique, stable, inexpensive, noninvasive, easy to use, oral/oropharyngeal cancer specific, rapid point-of-care (POC) risk assessment test based on these findings, 2) develop the application of this testing methodology to a point of care SolCD44 pretreatment prognostic test, and 3) explore the value of SolCD44 as a dynamic indicator of risk of recurrence in oral/oropharyngeal cancer. At the end of this project, the OncAlert rapid POC kit will consist of a simple, inexpensive, point of care test for oral/oropharyngeal cancer risk. In addition, confirmation of the independent prognostic value of SolCD44 in oral/oropharyngeal in recurrence free survival will form the basis for application to expand SolCD44 as an approved prognostic test for oral/oropharyngeal cancer. Finally we will explore the potential for SolCD44 to provide a dynamic indication of disease status in these cancers.